Introduction

In patients with ulcerative colitis (UC), total proctocolectomy with restorative ileal pouch-anal anastomosis (IPAA) is a definitive surgical treatment for refractory disease or colorectal dysplasia. A short rectal cuff is typically retained and anastomosed to the pouch, and may become inflamed over time, a condition referred to as cuffitis. The clinical relevance of cuffitis remain unexplored. In this study, we aimed to characterize the long-term disease course associated with histologic cuffitis.

Aims & Methods

Patients with UC who underwent total proctocolectomy and IPAA were prospectively followed in a comprehensive pouch clinic at a tertiary referral center for patients with inflammatory bowel diseases (IBD). We included all patients who underwent at least one pouch endoscopy with paired pouch and cuff biopsies between 2017 and 2024. Cuffitis was defined as a NANCY Index histologic score of 3-4, and pouchitis was defined as histologic subscore of PDAI³2. Outcomes assessed included documented inflammatory pouch flares, defined by clinical evaluation; antibiotics used due to pouch inflammation; and initiation of biologics. Associations were evaluated using Poisson regression to estimate incidence rate ratios (IRRs) and Fisher’s exact test for categorical comparisons.

Results

A total of 116 patients underwent 250 pouch endoscopies during the study period. Average age of the cohort was 50.4 (±14.9) and 59% were females. Histologic pouchitis was detected in 80 (68.9%), and cuffitis in 76 (65.5%) patients. Most patients had extensive disease prior to IPAA (n=105, 90.5%) and indication for surgery was refractory UC (n=94, 81.0%). Concurrent pouchitis and cuffitis were identified in 54 (46.5%) patients. Patients with histologic-proven cuffitis had a significantly higher incidence rate of subsequent disease flares(IRR 4.39, 95% CI: 2.26-9.86, p<0.001) and required more antibiotic courses (IRR 1.94, 95% CI: 1.11-3.62, p=0.027) compared to those who never developed cuffitis. These associations remained significant after adjusting for the presence of histologic pouchitis. No significant difference was observed in the initiation of biologics (p=0.81). Among patients with at least two endoscopies during follow-up and isolated cuffitis at baseline (n=61), 6 patients with isolated cuffitis further developed new-onset pouchitis, while 15 patients with isolated pouchitis subsequently developed cuffitis. The remaining 40 patients (65.5%) maintained the same inflammatory pattern over time.

Conclusion

Histologic-proven cuffitis is independently associated with adverse long-term outcomes in patients post-IPAA, including flares and repeated antibiotic use, even in the absence of pouchitis. The persistence of inflammation in the retained rectal cuff, representing a remnant of the previously diseased colonic mucosa, raises mechanistic questions about its potential role in modulating inflammatory activity of the pouch. These findings emphasize the clinical importance of evaluating the rectal cuff in patients post-IPAA. Routine histologic assessment of the cuff should be incorporated into post IPAA surveillance, and interventional studies are warranted to determine whether targeted treatment of cuffitis can mitigate pouch related morbidity.

Disclosure

Jacob E Ollech: Has received grant support from Pfizer, consulting fees from Takeda, and
speaker fees from Abbvie, Janssen, Pfizer, Takeda, Novartis, and Bristol Myers Squibb.
Iris Dotan: consultation fee or honorarium from: Abbott, Abbvie, Athos, Arena, Altman
Research, Cambridge Healthcare, Celltrion, Celgene/BMS, Eli-Lilly, Ferring, Falk Pharma, Food
Industries Organization, Gilead, Galapagos, Iterative Scopes, Integra Holdings, Janssen,
Neopharm, Pfizer, Rafa laboratories, Roche/Genentech, Sangamo, Sublimity, Sandoz, Takeda,
Wildbio. Grants: Altman Research, BMS, Pfizer